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Development of a high throughput-compatible assay for screening filamentous fungi

Award Number: F32AI145160
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/06/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2022

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Development of a high throughput-compatible assay for screening filamentous fungi - PROJECT SUMMARY A major obstacle in the development of mold-active antifungals is limited methodologies for high throughput screening with molds. Aspergillus fumigatus and Fusarium spp. are two common molds that cause invasive infections in immune-compromised patients. Despite current antifungal treatments, limited to only three unique classes of drugs, mortality rates of these infections are devastatingly high. In addition to the serious health threat molds pose to immune-compromised patients, molds cause infections in immune-competent individuals, particularly in the form of corneal infections, or fungal keratitis. Fungal keratitis is a leading cause of monocular blindness worldwide and only about half of patients with corneal infections caused by Aspergillus or Fusarium respond to treatment. The current state of fungal infections worldwide, combined with emerging resistance to current antifungal drugs, calls for novel classes of mold-active antifungals to combat these life- threatening infections. This proposal aims to fill a technical gap in the field by applying the adenylate kinase assay to filamentous fungi to perform high throughput screening. The adenylate kinase assay has been validated and successfully used for high throughput screening with yeast and bacteria and possesses several qualities that make it an excellent candidate for application to molds. We have shown that this assay reliably detects lysis of A. fumigatus and optimized conditions suitable for high throughput screening. In this proposal, our goal is to adapt this assay to Fusarium oxysporum, then perform screens with Aspergillus and Fusarium with multiple small molecule and natural product libraries. In addition to screening against wild type A. fumigatus, we will perform a repurposing screen of FDA-approved drugs using a strain harboring a common voriconazole resistance mechanism. In this way, we hope to identify novel classes of mold-active antifungal drugs, as well as drugs to be repurposed and expedited to clinical use to treat fungal infections.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$29,434 )
2023	2022	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	001	3	6/20/2023	NON-COMPETING CONTINUATION	-$8,794
2023	2022	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	3	1/18/2023	NON-COMPETING CONTINUATION	-$20,640
														Subtotal = -$29,434

Issue Date FY: 2022 ( Subtotal = $71,734 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	001	3	5/24/2022	NON-COMPETING CONTINUATION	$1,276
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	3	12/10/2021	NON-COMPETING CONTINUATION	$70,458
														Subtotal = $71,734

Issue Date FY: 2021 ( Subtotal = $68,562 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	001	2	2/11/2021	NON-COMPETING CONTINUATION	$1,116
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	2	12/3/2020	NON-COMPETING CONTINUATION	$67,446
														Subtotal = $68,562

Issue Date FY: 2020 ( Subtotal = $65,310 )
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	1	12/23/2019	NEW	$61,610
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	002	1	3/5/2020	NEW	$3,700
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	001	1	12/23/2019	NEW	$0
														Subtotal = $65,310

Grand Total All Awards = $176,172

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Development of a high throughput-compatible assay for screening filamentous fungi

Award Number: F32AI145160

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/06/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2022

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